Substituted amide derivatives having multimodal activity against pain

Abstract

The present invention relates to substituted amide derivatives having dual pharmacological activity towards both the sigma (σ) receptor, and the μ-opioid receptor, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

The invention claimed is: 
     
       1. A compound of general Formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         m is 1 or 2; 
         n is 0, 1 or 2; 
         p is 0, 1 or 2; 
         W is nitrogen or carbon; 
         X is a bond, —C(R x R x′ )—, C═O, —C(O)O— or —O—;
 wherein R x  is selected from the group consisting of halogen, —OR 15 , substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl and substituted or unsubstituted C 2-6  alkynyl; 
 R x′ is selected from the group consisting of hydrogen, halogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl and substituted or unsubstituted C 2-6  alkynyl; 
 R 15  is selected from the group consisting of hydrogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl and substituted or unsubstituted C 2-6  alkynyl; 
 
         R 1  is selected from the group consisting of substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl, substituted or unsubstituted C 2-6  alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl;
 wherein the cycloalkyl, aryl or heterocyclyl in R 1  if substituted, is substituted with one or more substituent/s selected from the group consisting of halogen, —R 11 , —OR 11 , —NO 2 , —NR 11 R 11′″ , NR 11 C(O)R 11′ , —NR 11 S(O) 2 R 11′ , —S(O) 2 NR 11 R 11′ , —NR 11 C(O)NR 11′ R 11″ , —SR 11 , —S(O)R 11 , S(O) 2 R 11 , —CN, haloalkyl, haloalkoxy, —C(O)OR 11 , —C(O)NR 11 R 11′ , —NR 11 S(O) 2 NR 11′ R 11″  and C(CH 3 ) 2 OR 11 ; 
 and wherein the cycloalkyl or non-aromatic heterocyclyl in R 1 , if substituted, may also be substituted with 
 
       
       
         
           
           
               
               
           
         
         
            or ═O; 
           wherein the alkyl, alkenyl or alkynyl in R 1 , if substituted, is substituted with one or more substituent/s selected from the group consisting of —OR 11 , halogen, —CN, haloalkyl, haloalkoxy, —SR 11 , —S(O)R 11 , and —S(O) 2 R 11 ; 
           wherein R 11 , R 11′  and R 11″  are independently selected from the group consisting of hydrogen, unsubstituted C 1-6  alkyl, unsubstituted C 2-6  alkenyl and unsubstituted C 2-6  alkynyl; 
           and wherein R 11′″  is selected from the group consisting of hydrogen, unsubstituted C 1-6  alkyl, unsubstituted C 2-6  alkenyl, unsubstituted C 2-6  alkynyl and -Boc; 
         
         R 2  is selected from the group consisting of hydrogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl, substituted or unsubstituted C 2-6  alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl;
 wherein the cycloalkyl, aryl or heterocyclyl in R 2 , if substituted, is substituted with one or more substituent/s selected from the group consisting of halogen, —R 12 , —OR 12 , —NO 2 , —NR 12 R 12′″ , NR 12 C(O)R 12′ , —NR 12 S(O) 2 R 12′ , —S(O) 2 NR 12 R 12′ , —NR 12 C(O)NR 12′ R 12″ , —SR 12 , —S(O)R 12 , S(O) 2 R 12 , —CN, haloalkyl, haloalkoxy, —C(O)OR 12 , —C(O)NR 12 R 12′ , —NR 12 S(O) 2 NR 12′ R 12″  and C(CH 3 ) 2 OR 12 ; 
 and wherein the cycloalkyl or non-aromatic heterocyclyl in R 2 , if substituted, may also be substituted with 
 
       
       
         
           
           
               
               
           
         
         
            or ═O; 
           wherein the alkyl, alkenyl or alkynyl in R 2 , if substituted, is substituted with one or more substituent/s selected from the group consisting of —OR 12 , halogen, —CN, haloalkyl, haloalkoxy, —SR 12 , —S(O)R 12 , and —S(O) 2 R 12 ; 
           wherein R 12 , R 12′  and R 12″  are independently selected from the group consisting of hydrogen, unsubstituted C 1-6  alkyl, unsubstituted C 2-6  alkenyl and unsubstituted C 2-6  alkynyl; 
           and wherein R 12′″  is selected from the group consisting of hydrogen, unsubstituted C 1-6  alkyl, unsubstituted C 2-6  alkenyl, unsubstituted C 2-6  alkynyl and -Boc; 
         
         R 3  is selected from the group consisting of substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl, substituted or unsubstituted C 2-6  alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, —NR 9 R 9′  and —CH 2 OR 9 ;
 wherein R 9  and R 9 ′ are independently selected from the group consisting of hydrogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl, substituted or unsubstituted C 2-6  alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; 
 
         R 4  and R 4′  are independently selected from the group consisting of substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl and substituted or unsubstituted C 2-6  alkynyl, 
         or R 4  and R 4′  together with the carbon atom to which they are attached, form a cycle of Formula (A) (with “●” marking the carbon atom to which R 4  and R 4′  are attached): 
       
       
         
           
           
               
               
           
         
         
           wherein 
           q is 0 or 1; 
           r is 0, 1 or 2; 
           Y is —CH 2 —, —N(R y )—, —S— or —O—; 
           R 8  and R 8′  are independently selected from the group consisting of hydrogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl and substituted or unsubstituted C 2-6  alkynyl; 
           or R 8  and R 8′  together with the carbon atom to which they are attached, form a C 3-6  cycloalkyl; 
           R y  is selected from the group consisting of hydrogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl and substituted or unsubstituted C 2-6  alkynyl; 
         
         R 5  and R 5′  are independently selected from the group consisting of hydrogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl, substituted or unsubstituted C 2-6  alkynyl, —CH 2 OR 10  and —C(O)OR 10 ;
 wherein R 10  is selected from the group consisting of hydrogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl and substituted or unsubstituted C 2-6  alkynyl; 
 
         R 6  and R 6′  are independently selected from the group consisting of hydrogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl and substituted or unsubstituted C 2-6  alkynyl; 
         R 7  and R 7′  are independently selected from the group consisting of hydrogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl and substituted or unsubstituted C 2-6  alkynyl; 
         and wherein 
       
       
         
           
           
               
               
           
         
          is selected from 
       
       
         
           
           
               
               
           
         
         wherein 
         the alkyl, alkenyl or alkynyl, other than those defined in R 1  or R 2 , if substituted, is substituted with one or more substituent/s selected from the group consisting of —OR 13 , halogen, —CN, haloalkyl, haloalkoxy, —SR 13 , —S(O)R 13 , and —S(O) 2 R 13 ;
 wherein R 13  is selected from hydrogen, unsubstituted C 1-6  alkyl, unsubstituted C 2-6  alkenyl, and unsubstituted C 2-6  alkynyl; 
 
         the aryl, heterocyclyl or cycloalkyl other than those defined in R 1  or R 2 , if substituted, is substituted with one or more substituent/s selected from the group consisting of halogen, —R 14 , —OR 14 , —NO 2 , —NR 14 R 14′″ , NR 14 C(O)R 14′ , —NR 14 S(O) 2 R 14′ , —S(O) 2 NR 14 R 14′ , —NR 14 C(O)NR 14′ R 14″ , —SR 14 , —S(O)R 14 , S(O) 2 R 14 , —CN, haloalkyl, haloalkoxy, —C(O)OR 14 , —C(O)NR 14 R 14′ , —NR 14 S(O) 2 NR 14′ R 14″  and C(CH 3 ) 2 OR 14 ; 
         and wherein the cycloalkyl or non-aromatic heterocyclyl, other than those defined in R 1  or R 2 , if substituted, may also be substituted with 
       
       
         
           
           
               
               
           
         
          or ═O;
 wherein R 14 , R 14′  and R 14″  are independently selected from hydrogen, unsubstituted C 1-6  alkyl, unsubstituted C 2-6  alkenyl, unsubstituted C 2-6  alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; 
 and wherein R 14′″  is selected from hydrogen, unsubstituted C 1-6  alkyl, unsubstituted C 2-6  alkenyl, unsubstituted C 2-6  alkynyl and -Boc; 
 
         optionally as a stereoisomer, a racemate or a mixture of at least two stereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof; 
         with the provisos that:
 —[CR 5 R 5′ ] m —X—(CR 6 R 6′ ) n —R 2  is not unsubstituted methyl; 
 or 
 R 1  is neither an unsubstituted nor an N-alkyl-substituted compound of the following formula: 
 
       
       
         
           
           
               
               
           
         
       
     
     
       2. The compound according to  claim 1 , wherein 
       
         
           
           
               
               
           
         
         and W is nitrogen or carbon. 
       
     
     
       3. The compound according to  claim 2 , wherein W is nitrogen. 
     
     
       4. The compound according to  claim 1 , wherein the compound is a compound of general formula (I 4′ ) 
       
         
           
           
               
               
           
         
         wherein 
         m′ is 0 or 1; 
         p is 0, 1 or 2; 
         W is nitrogen or carbon; 
         X is a bond, —C(R x R x′ )—, C═O, —C(O)O— or —O—;
 wherein R x  is selected from the group consisting of halogen, —OR 15 , substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl and substituted or unsubstituted C 2-6  alkynyl; 
 R x′  is selected from the group consisting of hydrogen, halogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl and substituted or unsubstituted C 2-6  alkynyl; 
 R 15  is selected from the group consisting of hydrogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl and substituted or unsubstituted C 2-6  alkynyl; 
 
         R 1  is selected from the group consisting of substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl, substituted or unsubstituted C 2-6  alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted monocyclic heterocyclyl and unsubstituted polycyclic heterocyclyl;
 wherein the cycloalkyl, aryl or heterocyclyl in R 1  if substituted, is substituted with one or more substituent/s selected from the group consisting of halogen, —R 11 , —OR 11 , —NO 2 , —NR 11 R 11′″ , NR 11 C(O)R 11′ , —NR 11 S(O) 2 R 11′ , —S(O) 2 NR 11 R 11′ , —NR 11 C(O)NR 11′ R 11″ , —SR 11 , —S(O)R 11 , S(O) 2 R 11 , —CN, haloalkyl, haloalkoxy, —C(O)OR 11 , —C(O)NR 11 R 11′ , —NR 11 S(O) 2 NR 11′ R 11″  and C(CH 3 ) 2 OR 11 ; 
 and wherein the cycloalkyl or non-aromatic heterocyclyl in R 1 , if substituted, may also be substituted with 
 
       
       
         
           
           
               
               
           
         
         
            or ═O; 
           wherein the alkyl, alkenyl or alkynyl in R 1 , if substituted, is substituted with one or more substituent/s selected from the group consisting of —OR 11 , halogen, —CN, haloalkyl, haloalkoxy, —SR 11 , —S(O)R 11 , and —S(O) 2 R 11 ; 
           wherein R 11 , R 11′  and R 11″  are independently selected from the group consisting of hydrogen, unsubstituted C 1-6  alkyl, unsubstituted C 2-6  alkenyl and unsubstituted C 2-6  alkynyl; 
           and wherein R 11′″  is selected from the group consisting of hydrogen, unsubstituted C 1-6  alkyl, unsubstituted C 2-6  alkenyl, unsubstituted C 2-6  alkynyl and -Boc; 
         
         R 2  is selected from the group consisting of substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl, substituted or unsubstituted C 2-6  alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl,
 wherein the cycloalkyl, aryl or heterocyclyl in R 2 , if substituted, is substituted with one or more substituent/s selected from the group consisting of halogen, —R 12 , —OR 12 , —NO 2 , —NR 12 R 12′″ , NR 12 C(O)R 12′ , —NR 12 S(O) 2 R 12′ , —S(O) 2 NR 12 R 12′ , —NR 12 C(O)NR 12′ R 12″ , —SR 12 , —S(O)R 12 , S(O) 2 R 12 , —CN, haloalkyl, haloalkoxy, —C(O)OR 12 , —C(O)NR 12 R 12′ , —NR 12 S(O) 2 NR 12′ R 12″  and C(CH 3 ) 2 OR 12 ; 
 and wherein the cycloalkyl or non-aromatic heterocyclyl in R 2 , if substituted, may also be substituted with 
 
       
       
         
           
           
               
               
           
         
         
            or ═O; 
           wherein the alkyl, alkenyl or alkynyl in R 2 , if substituted, is substituted with one or more substituent/s selected from the group consisting of —OR 12 , halogen, —CN, haloalkyl, haloalkoxy, —SR 12 , —S(O)R 12 , and —S(O) 2 R 12 ; 
           wherein R 12 , R 12′  and R 12″  are independently selected from the group consisting of hydrogen, unsubstituted C 1-6  alkyl, unsubstituted C 2-6  alkenyl and unsubstituted C 2-6  alkynyl; 
           and wherein R 12′″  is selected from the group consisting of hydrogen, unsubstituted C 1-6  alkyl, unsubstituted C 2-6  alkenyl, unsubstituted C 2-6  alkynyl and -Boc; 
         
         R 3  is selected from the group consisting of substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl, substituted or unsubstituted C 2-6  alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, —NR 9 R 9′  and —CH 2 OR 9 ;
 wherein R 9  and R 9 ′ are independently selected from the group consisting of hydrogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl, substituted or unsubstituted C 2-6  alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; 
 
         R 4  and R 4′  are independently selected from the group consisting of substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl and substituted or unsubstituted C 2-6  alkynyl, 
         or R 4  and R 4′ , together with the carbon atom to which they are attached, form a cycle of Formula (A), with “●” marking the carbon atom to which R 4  and R 4′  are attached: 
       
       
         
           
           
               
               
           
         
         
           wherein 
           q is 0 or 1 
           r is 0, 1 or 2 
           Y is —CH 2 —, —N(R y )—, —S— or —O—; 
           R 8  and R 8′  are independently selected from the group consisting of hydrogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl and substituted or unsubstituted C 2-6  alkynyl; 
           or R 8  and R 8′ , together with the carbon atom to which they are attached, form a C 3-6  cycloalkyl; 
           R y  is selected from the group consisting of hydrogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl and substituted or unsubstituted C 2-6  alkynyl; 
         
         R 5  and R 5′  are independently selected from the group consisting of hydrogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl, substituted or unsubstituted C 2-6  alkynyl, —CH 2 OR 10  and —C(O)OR 10 ;
 wherein R 10  is selected from the group consisting of hydrogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl and substituted or unsubstituted C 2-6  alkynyl; 
 
         R 5″  and R 5′″  are independently selected from the group consisting of hydrogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl, substituted or unsubstituted C 2-6  alkynyl, —CH 2 OR 10′  and —C(O)OR 10′ ;
 wherein R 10′  is selected from the group consisting of hydrogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl and substituted or unsubstituted C 2-6  alkynyl; 
 
         R 7  and R 7′  are independently selected from the group consisting of hydrogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl and substituted or unsubstituted C 2-6  alkynyl; 
         wherein 
         the alkyl, alkenyl or alkynyl, other than those defined in R 1  or R 2 , if substituted, is substituted with one or more substituent/s selected from the group consisting of —OR 13 , halogen, —CN, haloalkyl, haloalkoxy, —SR 13 , —S(O)R 13 , and —S(O) 2 R 13 ;
 wherein R 13  is selected from the group consisting of hydrogen, unsubstituted C 1-6  alkyl, unsubstituted C 2-6  alkenyl, and unsubstituted C 2-6  alkynyl; 
 
         the aryl, heterocyclyl or cycloalkyl other than those defined in R 1  or R 2 , if substituted, is substituted with one or more substituent/s selected from the group consisting of halogen, —R 14 , —OR 14 , —NO 2 , —NR 14 R 14′″ , NR 14 C(O)R 14′ , —NR 14 S(O) 2 R 14′ , —S(O) 2 NR 14 R 14′ , —NR 14 C(O)NR 14′ R 14″ , —SR 14 , —S(O)R 14 , S(O) 2 R 14 , —CN, haloalkyl, haloalkoxy, —C(O)OR 14 , —C(O)NR 14 R 14′ , —NR 14 S(O) 2 NR 14′ R 14″  and C(CH 3 ) 2 OR 14 ; 
         and wherein the cycloalkyl or non-aromatic heterocyclyl, other than those defined in R 1  or R 2 , if substituted, may also be substituted with 
       
       
         
           
           
               
               
           
         
          or ═O;
 wherein R 14 , R 14′  and R 14″  are independently selected from the group consisting of hydrogen, unsubstituted C 1-6  alkyl, unsubstituted C 2-6  alkenyl, unsubstituted C 2-6  alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; 
 and wherein R 14′″  is selected from the group consisting of hydrogen, unsubstituted C 1-6  alkyl, unsubstituted C 2-6  alkenyl, unsubstituted C 2-6  alkynyl and -Boc; 
 
         optionally as a stereoisomer, a racemate or a mixture of at least two stereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. 
       
     
     
       5. The compound according to  claim 1 , wherein
 X is a bond, C═O, —C(O)O— or —O—. 
 
     
     
       6. The compound according to  claim 5 , wherein X is a bond or —O—. 
     
     
       7. The compound according to  claim 1 , wherein R 1  is selected from the group consisting of substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl, substituted or unsubstituted C 2-6  alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted monocyclic heterocyclyl. 
     
     
       8. The compound according to  claim 7 , wherein R 1  is substituted or unsubstituted ethyl, substituted or unsubstituted isobutyl, substituted or unsubstituted phenyl, substituted or unsubstituted pyridine and substituted or unsubstituted thiazole. 
     
     
       9. The compound according to  claim 1 , wherein R 2  is selected from the group consisting of substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl, substituted or unsubstituted C 2-6  alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl. 
     
     
       10. The compound according to  claim 9 , wherein R 2  is selected from the group consisting of substituted or unsubstituted methyl, substituted or unsubstituted ethyl, substituted or unsubstituted isopropyl, substituted or unsubstituted isobutyl, —CF 3 , —CH 2 CF 3 , substituted or unsubstituted phenyl, substituted or unsubstituted pyridine, substituted or unsubstituted piperidine, substituted or unsubstituted morpholine and substituted or unsubstituted cyclopropyl. 
     
     
       11. The compound according to  claim 1 , wherein R 3  is selected from the group consisting of substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl, substituted or unsubstituted C 2-6  alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, —NR 9 R 9′  and —CH 2 OR 9 ;
 wherein R 9  and R 9 ′ are independently selected from the group consisting of hydrogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl, substituted or unsubstituted C 2-6  alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl. 
 
     
     
       12. The compound according to  claim 11 , wherein R 3  is substituted or unsubstituted ethyl. 
     
     
       13. The compound according to  claim 11 , wherein R 9  and R 9 ′ are independently selected from the group consisting of hydrogen, substituted or unsubstituted methyl, and substituted or unsubstituted ethyl. 
     
     
       14. The compound according to  claim 1 , wherein R 4  and R 4′  are independently selected from the group consisting of substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl and substituted or unsubstituted C 2-6  alkynyl. 
     
     
       15. The compound according to  claim 14 , wherein R 4  and R 4′  are both substituted or unsubstituted methyl. 
     
     
       16. The compound according to  claim 1 , wherein R 4  and R 4′ , together with the carbon atom to which they are attached, form a cycle of Formula (A). 
     
     
       17. The compound according to  claim 16 , wherein the cycle of Formula (A) is selected from the group consisting of substituted or unsubstituted tetrahydropyran, substituted or unsubstituted tetrahydrothiopyran, substituted or unsubstituted cyclopropyl, substituted or unsubstituted cyclobutyl, substituted or unsubstituted oxetane, substituted or unsubstituted cyclohexyl and substituted or unsubstituted piperidine. 
     
     
       18. The compound according to  claim 1 , wherein the compound is selected from the group consisting of:
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-phenylpropionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(2-chlorophenyl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(2-methoxyphenyl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(2-fluorophenyl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(3-fluorophenyl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(5-fluoropyridin-2-yl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(5-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(4-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(5-(trifluoromethyl)pyridin-3-yl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(5-fluoropyridin-3-yl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-3-yl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(pyridin-4-yl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(1-phenylethyl)propionamide 
 N-benzyl-N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-isobutylpropionamide 
 N-((4-(4-benzylpiperazin-1-yl)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-N-(pyridin-2-yl)propionamide 
 N-((9-(4-benzylpiperazin-1-yl)-6-oxaspiro[4.5]decan-9-yl)methyl)-N-(pyridin-2-yl)propionamide 
 N-((3-(4-benzylpiperazin-1-yl)oxetan-3-yl)methyl)-N-phenylpropionamide 
 N-((1-(4-benzylpiperazin-1-yl)cyclohexyl)methyl)-N-phenylpropionamide 
 N-((1-(4-phenethylpiperazin-1-yl)cyclohexyl)methyl)-N-phenylpropionamide 
 N-((1-(4-phenethylpiperazin-1-yl)cyclohexyl)methyl)-N-(pyridin-2-yl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)-1-methylpiperidin-4-yl)methyl)-N-phenylpropionamide 
 N-((1-methyl-4-(4-phenethylpiperazin-1-yl)piperidin-4-yl)methyl)-N-phenylpropionamide 
 N-((4-(4-benzylpiperazin-1-yl)-1-methylpiperidin-4-yl)methyl)-N-(4-ethoxyphenyl)propionamide 
 N-(2-(4-benzylpiperazin-1-yl)-2-methylpropyl)-N-phenylpropionamide 
 N-(2-methyl-2-(4-phenethylpiperazin-1-yl)propyl)-N-phenylpropionamide 
 N-(2-methyl-2-(4-phenethylpiperazin-1-yl)propyl)-N-(pyridin-2-yl)propionamide 
 N-((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)-N-phenylpropionamide 
 N-((1-(4-phenethylpiperazin-1-yl)cyclopropyl)methyl)-N-phenylpropionamide 
 N-((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)-N-(pyridin-2-yl)propionamide 
 N-((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)-N-(pyridin-4-yl)propionamide 
 N-((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)-N-(2-methoxyphenyl)propionamide 
 N-((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)-N-(5-fluoropyridin-2-yl)propionamide 
 N-((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)-N-(2-chlorophenyl)propionamide 
 N-((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)-N-(2-fluorophenyl)propionamide 
 N-((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)-N-(pyridin-3-yl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-methoxy-N-phenylacetamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(pyridin-2-yl)thiophene-2-carboxamide 
 N-((4-(4-isobutylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-methoxy-N-(6-(trifluoromethyl)pyridin-2-yl)acetamide 
 N-((4-(4-isobutylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)acetamide 
 N-((4-(4-benzylpiperazin-1-yl)-1-methylpiperidin-4-yl)methyl)-N-phenylthiazole-2-carboxamide 
 N-((4-(4-benzylpiperazin-1-yl)-1-methylpiperidin-4-yl)methyl)-N-phenylthiophene-2-carboxamide 
 N-(2-(4-benzylpiperazin-1-yl)-2-methylpropyl)-2-methoxy-N-phenylacetamide 
 N-(2-methyl-2-(4-phenethylpiperazin-1-yl)propyl)-N-phenylfuran-2-carboxamide 
 3-ethyl-1-(2-methyl-2-(4-phenethylpiperazin-1-yl)propyl)-1-phenylurea 
 N-((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)-2-methoxy-N-phenylacetamide 
 N-((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)-N-(pyridin-2-yl)thiophene-2-carboxamide 
 1-(2-(4-benzylpiperazin-1-yl)-2-methylpropyl)-3-ethyl-1-phenylurea 
 1((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-3-ethyl-1-(pyridin-2-yl)urea 
 3-ethyl-1((1-(4-phenethylpiperazin-1-yl)cyclohexyl)methyl)-1-phenylurea 
 2-methoxy-N-(2-methyl-2-(4-phenethylpiperazin-1-yl)propyl)-N-phenylacetamide 
 1((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)-3-ethyl-1-phenylurea 
 3-ethyl-1((1-(4-phenethylpiperazin-1-yl)cyclopropyl)methyl)-1-phenylurea 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(2-hydroxyphenyl)propionamide 
 N-((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)-N-(2-hydroxyphenyl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(pyridin-2-yl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(3-cyanophenyl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetranydro-2H-pyran-4-yl)methyl)-N-(3-cyanopyridin-2-yl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(3 (thfluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(3-cyano-6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-cyano-5-fluoropyridin-2-yl)propionamide 
 N-(3-cyanopyridin-2-yl)-N-((4-(4-isobutylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)propionamide 
 N-((4-(4-isobutylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(3-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-N-(3-fluoropyridin-2-yl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-N-(6-cyanopyridin-2-yl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-N-(3-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-N-(3-cyanopyridin-2-yl)propionamide 
 N-(2-(4-(2-fluorophenethyl)piperazin-1-yl)-2-methylpropyl)-N-(3-fluoropyridin-2-yl)propionamide 
 N-(2-(4-(2-(3-fluoropyridin-2-yl)ethyl)piperazin-1-yl)-2-methylpropyl)-N-(pyridin-2-yl)propionamide 
 N-(2-fluorophenyl)-N-(2-(4-(2-(3-fluoropyridin-2-yl)ethyl)piperazin-1-yl)-2-methylpropyl)propionamide 
 N-(2-(4-(2-(3-fluoropyridin-2-yl)ethyl)piperazin-1-yl)-2-methylpropyl)-N-phenylpropionamide 
 N-(3-fluoropyridin-2-yl)-N-(2-(4-(2-isopropoxyethyl)piperazin-1-yl)-2-methylpropyl)propionamide 
 N-(3-fluoropyridin-2-yl)-N-(2-(4-isobutylpiperazin-1-yl)-2-methylpropyl)propionamide 
 N-(3-fluoropyridin-2-yl)-N-(2-(4-isopentylpiperazin-1-yl)-2-methylpropyl)propionamide 
 N-((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)-N-(2-(trifluoromethyl)pyridin-3-yl)propionamide 
 N-((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)-N-(3-fluoropyridin-2-yl)propionamide 
 N-((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)-N-(4-(trifluoromethyl)pyridin-3-yl)propienarnide 
 N-((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)-N-(3-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)-N-(3-cyanopyridin-2-yl)propionamide 
 N-((4-4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(4-fluorophenyl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(3-fluoropyridin-2-yl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-cyanopyridin-2-yl)propionamide 
 N-(6-cyanopyridin-2-yl)-N-((4-(4-isobutylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)propionamide 
 N-(6-cyanopyridin-2-yl)-N-(4-(4-isopentylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)propionamide 
 N-(6-cyanopyridin-2-yl)-N-((4-(4-isobutylpiperazin-1-yl)-2.2-dimethyltetrahydro-2H-pyran-4-yl)methyl)propionamide 
 N-(6-cyanopyridin-2-yl)-N-(4-(4-isopentylpiperazin-1-yl)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)propionamide 
 N-((9-(4-benzylpiperazin-1-yl)-6-oxaspiro[4.5]decan-9-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(1-benzylpipendin-4-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)-N-(6-(trifluoromethyl)pyridin-2-y1)propionamide 
 N-((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)-N-(thiazol-2yl)propionamide 
 N-((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)-N-(5-fluoropyridin-3-yl)propionamide 
 N-((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)-N-(5-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)-N-(3-fluorophenyl)propionamide 
 N-((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)-N-(3-cyanophenyl)propionannide 
 N-((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)-N-(6-cyanopyridin-2-yl)propionamide 
 N-benzyl-N-((1-(4-benzylpiperazin-1-yl)cyclopropyl)methyl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-ethylpropionamide 
 N-((4-(4-(3-fluorobenzylpiperazin-1-yl)tetranydro-2H-pyran-4-yl)methyl)-N-phenylpropionamide 
 N-phenyl-N-((4-(4-(pyridin-3-ylmethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)propionamide 
 N-phenyl-N-((4-(4-(pyridin-2-ylmethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)propionamide 
 N-phenyl-N-((4-(4((6-(trifluoromethyl)pyridin-3-yl)methyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)propionamide 
 N-((4-(4-(2-fluorobenzyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-phenylpropionamide 
 N-((4(4-(4-fluorobenzyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-phenylpropionamide 
 N-phenyl-N-((4-(4-(pyridin-4-ylmethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)propionamide 
 N-((4-(4-((5-fluoropyridin-3-yl)methyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-phenylpropionamide 
 N-((4-(4-(3,4-difluorobenzyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-phenylpropionamide 
 N-((4-(4-((6-methoxypyridin-3-yl)methyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-phenylpropionamide 
 N-((4-(4-(3-fluorobenzyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(pyridin-2-yl)propionamide 
 N-((4-(4-(4-fluorobenzyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(pyridin-2-yl)propionamide 
 N-((4-(4-(1-methoxypropan-2-yl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-phenyl-N-((1-(4((6-(trifluoromethyl)pyridin-3-yl)methyl)piperazin-1-yl)cyclopropyl)methyl)propionamide 
 N-phenyl-N-((1-(4-(pyridin-2-ylmethyl)piperazin-1-yl)cyclopropyl)methyl)propionamide 
 N-((1-(4-(4-acetamidobenzyl)piperazin-1-yl)cyclopropyl)methyl)-N-phenylpropionamide 
 N-((1-(4-(3-fluorobenzyl)piperazin-1-yl)cyclopropyl)methyl)-N-phenylpropionamide 
 N-((1-(4-(3,4-difluorobenzyl)piperazin-1-yl)cyclopropyl)methyl)-N-phenylpropionamide 
 N-((1-(4-(2-fluorobenzyl)piperazin-1-yl)cyclopropyl)methyl)-N-phenylpropionamide 
 N-phenyl-N-((1-(4-(pyridin-3-ylmethyl)piperazin-1-yl)cyclopropyl)methyl)propionamide 
 N-((1-(4-(3-fluoropyridin-2-yl)methyl)piperazin-1-yl)cyclopropyl)methyl)-N-phenylpropionamide 
 N-((1-(4-((5-fluoropyridin-2-yl)methyl)piperazin-1-yl)cyclopropyl)methyl)-N-phenylpropionamide 
 N-((1-(4-((5-fluoropyridin-3-yl)methyl)piperazin-1-yl)cyclopropyl)methyl)-N-phenylpropionamide 
 N-((1-(4-isobutylpiperazin-1-yl)cyclopropyl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((1-(4-isopentylpiperazin-1-yl)cyclopropyl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-methyl-4-((4-(4-((N-phenylpropionamido)methyl)tetrahydro-2H-pyran-4-yl)piperazin-1-yl)methyl)benzamide 
 N-((4-(4-phenethylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-phenylpropionamide 
 N-((4-(4-(2-oxo-2-(piperidin-1-yl)ethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-phenylpropionamide 
 N-((4-(4-phenethylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((3-(4-phenethylpiperazin-1-yl)oxetan-3-yl)methyl)-N-phenylpropionamide 
 N-((1-(4-(4-fluorobenzyl)piperazin-1-yl)cyclopropyl)methyl)-N-phenylpropionamide 
 N-methyl-4-(4-1-((N-phenylpropionamido)methyl)cyclopropyl)piperazin-1-yl)methyl)benzamide 
 N-((1-(4-(2-oxo-2-(piperidin-1-yl)ethyl)piperazin-1-yl)cyclopropyl)methyl)-N-phenylpropionamide 
 N-((4-(4-(1-phenylethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(1-phenylethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(pyridin-2-yl)propionamide 
 N-((4-(4-isobutylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-phenylpropionamide 
 N-((4-(4-isobutylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-isopentylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(2-isopropoxyethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-sec-butylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(2-ethoxyethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(2-(trifluoromethoxy)ethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(2-isobutoxyethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(2-(2,2,2-trifluoroethoxy)ethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 ethyl 3-(4-(4((N-(6-(trifluoromethyl)pyridin-2-yl)propionamido)methyl)tetrahydro-2H-pyran-4-yl)piperazin-1-yl)propanoate 
 N-((4-(4-(3-methoxypropyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-4-propylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-butylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(2-hydroxyethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(2-phenoxyethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(3-ethoxypropyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-isobutylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(pyridin-2-yl)propionamide 
 N-((4-(4-(2-isopropoxyethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(pyridin-2-yl)propionamide 
 N-((4-(4-isopentylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(pyridin-2-yl)propionamide 
 N-((4-(4-sec-butylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(pyridin-2-yl)propionamide 
 N-(3-fluoropyridin-2-yl)-N-((4-(4-isopentylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)propionamide 
 N-((4-(4-(2-ethoxyethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(3-fluoropyridin-2-yl)propionamide 
 N-(3-fluoropyridin-2-yl)-N-((4-(4-(2-isopropoxyethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)propionamide 
 N-(3-fluoropyridin-2-yl)-N-((4-(4-isobutylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)propionamide 
 N-((4-(4-isopentylpiperazin-1-yl)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4(4-isobutylpiperazin-1-yl)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(2-isopropoxyethyl)piperazin-1-yl)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-sec-butylpiperazin-1-yl)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(2-isopropoxyethyl)piperazin-1-yl)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-N-(pyridin-2-yl)propionamide 
 N-((4-(4-isopentylpiperazin-1-yl)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-N-(pyridin-2-yl)propionamide 
 N-((4-(4-(2-ethoxyethyl)piperazin-1-yl)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-N-(pyridin-2-yl)propionamide 
 N-((4-(4-isobutylpiperazin-1-yl)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-N-(pyridin-2-yl)propionamide 
 N-(3-fluoropyridin-2-yl)-N-((4-(4-(2-isopropoxyethyl)piperazin-1-yl)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)propionamide 
 N-(3-fluoropyridin-2-yl)-N-((4-(4-isopentylpiperazin-1-yl)-2,2-dmethyltetrahydro-2H-pyran-4-yl)methyl)propionamide 
 N-((4-(4-(2-ethoxyethyl)piperazin-1-yl)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-N-(3-fluoropyridin-2-yl)propionamide 
 N-(3-fluoropyridin-2-yl)-N-((4-(4-isobutylpiperazin-1-yl)-2,2-dimethyltetranydro-2H-pyran-4-yl)methyl)propionamide 
 N-(6-cyanopyridin-2-yl)-N-((4-(4-(2-ethoxyethyl)piperazin-1-yl)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)propionamide 
 N-(6-cyanopyridin-2-yl)-N-((4-(4-(2-isopropoxyethyl)piperazin-1-yl)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)propionamide 
 N-((9-(4-isopentylpiperazin-1-yl)-6-oxaspiro[4.5]decan-9-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((9-(4-(2-isopropoxyethyl)piperazin-1-yl)-6-oxaspiro[4.5]decan-9-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((9-(4-isobutylpiperazin-1-yl)-6-oxaspiro[4.5]decan-9-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((9-(4-(2-ethoxyethyl)piperazin-1-yl)-6-oxaspiro[4.5]decan-9-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(1-(2-ethoxyethyl)piperidin-4-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(1-isobutylpiperidin-4-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoremethyl)pyridin-2-yl)propionamide 
 N-((1-(4-(2-isopropoxyethyl)piperazin-1-yl)cyclopropyl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 methyl 2-phenyl-2-(4-(4((N-(pyridin-2-yl)propionamido)methyl)tetrahydro-2H-pyran-4-yl)piperazin-1-yl)acetate 
 N-((4-(4-(2-hydroxy-1-phenylethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(pyridin-2-yl)propionamide 
 N-((4-(4-(1-(4-fluorophenyl)ethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(2-cyclopropoxyethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(2-morpholinoethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(2-methoxyethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(2-(2-hydroxy-2-methylpropoxy)ethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(2-propoxyethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methy)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(2-hydroxy-2-methylpropyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(2-(2-fluoro-2-methylpropoxy)ethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(2-fluoro-2-methylpropyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(2-Methoxy-2-methylpropyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(2-(3-Fluoropyridin-2-yl)ethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(2-hydroxy-2-phenylethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(2-hydroxy-1-phenylethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)piperidin-4-yl)methyl)-N-phenylpropionamide
 optionally as a stereoisomer, a racemate or a mixture of at least two stereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. 
 
 
     
     
       19. The compound according to  claim 1 , wherein the compound is selected from the group consisting of:
 N-((4-(5-benzylhexehydropyrrolo[3,4-c]pyrrol-2(1H)-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoremethyl)pyridin-2-yl)propionamide 
 N-((1(4-benzylpiperazin-1-yl)cyclobutyl)methyl)-N-(6-trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-benzylpiperazin-1-yl)tetrahydro-2H-thiopyran-4yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(5-isobutylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(5-(2-ethoxyethyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(2-(pyridin-3-yl)ethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((1-(4-(2-ethoxyethyl)piperazin-1-yl)cyclobutyl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((1-(4-isobutylpiperazin-1-yl)cyclobutyl)methyl)-N-(6-(trifluoremethyl)pyridin-2-yl)propionamide 
 N-((4-(4-isobutylpiperazin-1-yl)tetrahydro-2H-thiopyran-4-yl)methyl-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(2-ethoxyethyl)piperazin-1-yl)tetrahydro-2-H-thiopyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide 
 N-((4-(4-(2-(pyridin-4-yl)ethyl)piperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-N-(6-(trifluoromethyl)pyridin-2-yl)propionamide
 optionally as a stereoisomer, a racemate or in form of a mixture of at least two stereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. 
 
 
     
     
       20. A process for the preparation of the compound of Formula (I) as defined in  claim 1 , wherein the process comprises reacting a compound of Formula (VIII) 
       
         
           
           
               
               
           
         
         with a compound of formula (Xa) through an alkylation reaction or (Xb) through a reductive amination reaction 
       
       
         
           
           
               
               
           
         
         or wherein the process comprises an acylation reaction of a compound of formula Vb 
       
       
         
           
           
               
               
           
         
         with an acyl halide of formula VIa or with an anhydride of formula VIb, 
       
       
         
           
           
               
               
           
         
         or wherein the process comprises treating compounds of formula Xb 
       
       
         
           
           
               
               
           
         
         with a reagent of formula Xb with a reagent of formula IVa 
       
       
         
           
           
               
               
           
         
       
     
     
       21. A process for the preparation of the compound of Formula (I) according to  claim 1 , employlng a compound of Formula IIa, IIb, IIIa, IIIb, IVa, IVb, Va, Vb, VIa, VIb, VIc, VII, VIII, IXa, IXb, Xa, Xb, XI, XII, XIIIa, XIIIb, XIVa, XIVb, XV, XVIa or XVIb: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
       22. A pharmaceutical composition which comprises the compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle. 
     
     
       23. A method of treating pain in a subject in need thereof, comprising administration of an effective amount of the compound according to  claim 1 . 
     
     
       24. The method according to  claim 23 , wherein the pain is selected from the group consisting of medium to severe pain, visceral pain, chronic pain, cancer pain, migraine, inflammatory pain, acute pain, neuropathic pain, allodynia, and hyperalgesia. 
     
     
       25. The compound according to  claim 1 , wherein the compound is in the form of an enantiomer or a diastereomer or in the form of a mixture of enantiomers and/or diastereomers, in any mixing ratio. 
     
     
       26. The compound according to  claim 4 , wherein the compound is in the form of an enantiomer or a diastereomer or in the form of a mixture of enantiomers and/or diastereomers, in any mixing ratio. 
     
     
       27. The compound according to  claim 18 , wherein the compound is in the form of an enantiomer or a diastereomer or in the form of a mixture of enantiomers and/or diastereomers, in any mixing ratio. 
     
     
       28. The compound according to  claim 19 , wherein the compound is in the form of an enantiomer or a diastereomer or in the form of a mixture of enantiomers and/or diastereomers, in any mixing ratio.